Nb carriers are used to protect healthy tissues from drugs/toxins administered systemically, increase the solubilization of hydrophobic drugs, and increase the drug concentration in one dose, subsequently decreasing the number of repetitive doses [8]. == Figure 2. (small in size, low immunogenicity and a short half-life). Thus, the use of nanobodies in cancer practices may overcome the challenges experienced with using traditional antibodies. In this review, we discuss (1) the challenges with antibody usage and the superior qualities of nanobodies; (2) the use of antibodies and nanobodies in cancer imaging, diagnosis, drug delivery and therapy (surgery, radiotherapy, chemotherapy and immunotherapy); and (3) the potential improvements in oncology practices due to the use of nanobodies as compared to antibodies. Keywords:cancer, antibodies, nanobodies, imaging, diagnosis and therapies == 1. Cancer == Cancer is a complex disease, which is characterized by uncontrolled cell growth, the dysregulation of apoptosis, invasion, angiogenesis and metastasis [1,2]. Unfortunately, cancer incidence and mortality rates are drastically increasing [1]. Globally, there were approximately 18 million (mil) new cancer cases in 2018, and the cancer burden is expected to increase to 2937 mil new cases by 2040 [1,3]. Commonly diagnosed cancers include lung, female breast, colorectal and prostate cancer [1,3]. Worldwide, cancer is responsible for one in six fatalities [1]. In 2018, 9.6 mil cancer patients succumbed to the disease, with lung cancer being responsible for round 18.4% of cancer-associated deaths [1,3]. The most prevalent malignancies in children (<15 years) are leukemias, lymphomas and brain and nervous system cancers, whereas in older patients (1559 years), it is breast, liver and lung cancers [4,5]. In men and women (074 years), the risk of developing cancer is 22.4 and 18.2%, respectively [4,6]. The highest risk is for lung, breast, prostate and colorectal cancer [4,6]. The most commonly diagnosed cancers in men are lung (1.37 mil) and prostate PF-04554878 (Defactinib) (1.28 mil) cancers, whereas in women, it is breast (2.09 mil) and lung (0.72 mil) cancers [4,6]. In men and women (074 years), the risk of cancer mortality is 12.7 and 8.7%, respectively [4,6]. Pancreatic, lung, liver and intrahepatic bile duct cancers have the highest mortality rates, whereas thyroid, prostate and bladder cancers have a lower death rate [4,6]. Cancer is a serious health concern; therefore, the development of new techniques to visualize, diagnose and treat cancer is imperative. == 2. Antibodies == In humans, antibodies (Abs)/immunoglobulins (Igs: example IgG) are produced by the immune system as a defense against foreign bodies [7]. Abs have complex and highly conserved structures comprising of two identical heavy and two identical light chains, which are linked by disulfide bonds as well as non-covalent interactions [7]. The antigen-binding site contains three loops within the variable heavy (VH) domain and three variable loops within the variable light (VL) domain [7]. For decades, Abs have been generated and used in systemic cancer therapy to inhibit growth factors or receptors that contribute to cancer progression [7]. The three mechanisms that Abs use to target cancer cells are destruction by immune cells, changes in biological processes and the delivery of cytotoxic agents [7]. Although Abs have been beneficial in visualizing, diagnosing and treating cancer, there are several limitations with the use of Abs [7]. Firstly, high levels of immunogenicity (Table 1) decrease the efficacy of Abs. In patients, murine Abs stimulate an immunogenic response resulting in human anti-mouse Ab production, which neutralizes the Abs function by targeting murine idiotopes [7]. In an attempt Rabbit polyclonal to FAK.This gene encodes a cytoplasmic protein tyrosine kinase which is found concentrated in the focal adhesions that form between cells growing in the presence of extracellular matrix constituents. to decrease immunogenicity, chimeric Abs were developed [7]. These Abs contain human heavy and PF-04554878 (Defactinib) light chain regions as well as PF-04554878 (Defactinib) murine variable domains [7]. Chimeric Abs also stimulate an immunogenic response that generates human anti-chimeric Abs [7]. However, the immunogenicity of chimeric Abs (30%) is much lower than that of murine Abs (5075%) [7]. Additionally, the antigen-binding VH and VL loops can be grafted into a human IgG Ab to further decrease immunogenicity [7]. == Table 1. == A comparison between conventional PF-04554878 (Defactinib) antibodies and nanobodies. The large size of conventional Abs (150 kDa and 14.2 nm 8.2 nm 3.8 nm dimensions) restricts its penetration into tumor tissue (Table 1) [7,8]. Previous in vivo studies have demonstrated that in one gram of solid tumor, there is approximately 0.0010.01% of the injected Ab present, indicating the low level of penetration [7]. Additionally, poor penetration may be due to high affinity Abs binding strongly to the first antigen encountered [7]. Conventional Abs are fragile (Table 1), which limits treatment administration to intravenous or subcutaneous injections [7]. Moreover, due to the Abs complex structure and post-translational modifications, they are mostly expressed in mammalian cells; therefore, large-scale production is expensive (Table 1) [7]. In an attempt to overcome the limitations of monoclonal Abs (mAbs), the antigen-binding fragment (Fab, ~50 kDa), variable fragment (Fv, ~15 kDa) and single-chain Fv (scFv, ~30 kDa) were developed [8,9]. In comparison to mAbs, mAb-derived fragments are smaller in size, cleared faster and possess improved.